A major focus of drug addiction research has been on the neurocircuitry that mediates immediate positively reinforcing, or “rewarding,” properties of drugs. However, it has become increasingly clear that progression to addiction also involves a shift to negatively reinforced drug seeking and taking, where drugs are pursued for their ability to alleviate aversive emotional states. Stress has emerged as an important trigger of relapse, and the neural systems that process stressful stimuli and coordinate psychological and physiological responses to them have become increasingly recognized as important factors that maintain the addicted state. Hypothalamic as well as extrahypothalamic corticotropin releasing factor (CRF, also known as CRH) has received extensive attention as a mediator in this context, and constitutes a prototype for a “stress-related neuropeptide” of critical importance for addictive processes (Heilig and Koob, 2007; Koob and Volkow, 2010; Koob and Zorrilla, 2010). Other neuropeptides with established roles in linking stress and addiction-related behavior include dynorphin (Bruchas et al., 2010) and neuropeptide Y (NPY) (Heilig et al., 2010). More recently, however, additional neuropeptides including the urocortins (Ucn), neuropeptide S (NPS), nociceptin/orphanin FQ
